Obesity, the Gut Microbiome, and Cancer Risk: Inflammatory Crosstalk and Therapeutic Opportunities

Obesity is a well-established risk factor for at least 13 types of cancer, including colorectal, breast, endometrial, and hepatocellular carcinoma. Among the driving mechanisms, metainflammation, the chronic, low-grade inflammatory state induced by excess adipose tissue, acts as a critical mediator of oncogenesis. Gut microbiome dysbiosis, a hallmark of obesity, further compounds this risk by shifting immune cell metabolism toward a pro-inflammatory state and amplifying adipose tissue-driven inflammation. Conversely, a balanced microbiome produces protective metabolites — notably short-chain fatty acids (SCFAs), that exert anti-inflammatory effects and help mitigate this pro-tumorigenic environment.Nutritional oncology offers a promising avenue to interrupt this cycle. Dietary interventions, including prebiotics, probiotics, polyphenols, and fermented foods, may restore gut microbiome balance and reduce obesity-driven cancer risk. GLP-1 receptor agonists have also emerged as potent metabolic modulators that may lower the risk of specific obesity-related malignancies, though caution remains warranted for certain cancer types.Beyond individual health impacts, maternal obesity during pregnancy may program the offspring’s gut microbiome and immune development, elevating long-term susceptibility to metabolic disease and cancer, a transgenerational dimension that warrants dedicated scientific attention.Despite growing mechanistic understanding, critical gaps remain. It is unclear whether nutritional and lifestyle interventions that restore microbial diversity can sufficiently reverse the pro-inflammatory, pro-tumorigenic state in obese individuals, or whether pharmacological support is required. Similarly, the extent to which GLP-1 receptor agonists may modulate cancer risk through gut microbiota restoration and inflammation attenuation remains poorly characterized, and caution is warranted for specific cancer types. Equally underexplored is how maternal obesity and gut dysbiosis during pregnancy program offspring susceptibility to metabolic disease and cancer across the life course. This Research Topic aims to gather high-quality original research, systematic reviews, and clinical perspectives that advance our understanding of the nutritional, microbial, and metabolic drivers of obesity-related cancer risk, with a particular focus on actionable, evidence-based intervention strategies.We welcome submissions addressing, but not limited to, the following themes:● Metainflammation and oncogenesis: How gut dysbiosis-derived metabolites, including short-chain fatty acids (SCFAs) and lipopolysaccharides, modulate systemic inflammatory signaling pathways to promote or inhibit cancer initiation and recurrence, and whether lifestyle-driven weight loss can reverse this pro-tumorigenic state.● Nutritional and dietary modulators: The role of dietary patterns, macro/micronutrients, prebiotics, probiotics, polyphenols, and fermented foods in reshaping gut microbial composition, restoring barrier integrity, and reducing obesity-driven cancer risk.● Pharmacological metabolic interventions: The impact of GLP-1 receptor agonists on gut microbiota composition and systemic inflammation, their potential role in modifying cancer risk across specific malignancy types, and possible synergies with standard cancer treatments.● Obesity, the tumor microenvironment, and therapy resistance: How obesity-driven dysbiosis and immune remodeling alter the tumor microenvironment and influence the efficacy of immunotherapy or chemotherapy, reflecting the systemic crosstalk between metabolic dysfunction and oncogenesis.● Life-course and intergenerational perspectives: How maternal obesity and associated gut dysbiosis during pregnancy program the offspring’s immune system and early-life microbial colonization, shaping long-term susceptibility to metabolic disease and cancer. We particularly welcome studies investigating whether pre-conception metabolic optimization, including weight loss and dysbiosis correction, can mitigate this inherited risk. Topic editors: Fabia De Oliveira Andrade, Leena Hilakivi-Clarke Source: https://www.frontiersin.org/research-topics/82603/obesity-the-gut-microbiome-and-cancer-risk-inflammatory-crosstalk-and-therapeutic-opportunities